Recent insights into the CMS functions of the adenosine A2A receptor, its remarkable anatomical specificity for the basal ganglia, refinements in A2A receptor pharmacology and intriguing environmental clues have all converged to markedly enhance the potential of A2A antagonists as a novel therapeutic strategy for Parkinson's disease (PD). To achieve the proposal's major goal of facilitating the translation of advances in A2A receptor biology into well-designed clinical trials for PD, we propose holding an authoritative international conference that systematically covers the promise of A2A antagonists for PD - from basic science to preclinical and clinical studies. The conference, entitled "Targeting A2A adenosine receptors in Parkinson's disease", is planned for May 17-19 in Boston and will be hosted by Massachusetts General Hospital and its Mass General Institute for Neurodegenerative Disease. The event follows four years after our similarly focused meeting, and is designed to build on the momentum achieved through subsequent basic science and clinical advances. For example, recent laboratory insights into the heteromeric interactions of A2A with D2 dopamine and mGluS glutamate receptors, and clinical trial outcomes demonstrating antiparkinsonian efficacy of an A2A antagonist have created new opportunities for further therapeutic progress for PD and other CMS disorders. The conference sessions are organized over sequential themes: 1) fundamentals of A2A receptor biology, 2) A2A in basal ganglia physiology, 3) basis for the symptomatic motor benefits of A2A antagonists, 4) potential neuroprotective effects of caffeine and more specific A2A antagonists, 5) potential anti-dyskinetic effects of antagonists, 6) A2A receptors in non-motor CMS systems affecting sleep/mood/psychosis/addiction, and 7) translating these insights into effective, safe clinical trials for PD. Presentations from a diverse mix of established and young investigators (supported by a travel fellowship program for minority/underrepresented scientists), together with participation from a range of attendees spanning academia and industry will foster a fruitful exchange of information and ideas. This educational forum will extend well beyond the conference with the publication of its proceedings. Thus this timely conference is designed to catalyze the development of A2A antagonists as a novel multi-faceted treatment strategy for Parkinson's disease and related CMS disorders. [unreadable] [unreadable] [unreadable]